Bicyclic pyrazines having from six to ten carbon atoms in the hydrocarbon ring

ABSTRACT

WHEREIN Y IS (-CH2-)N, N IS AN INTEGER FROM 1 TO 5, AND R1, R2, R3, R4, R5, R6, R7, AND R8 AR THE SAME OR DIFFERENT AND REPRESENT HYDROGEN, OR ALKYL; THE PRODUCTS SO PRODUCED; FLAVORING AND FLAVOR-ENHANCING COMPOSITIONS CONTAINING SUCH BICYCLIC PYRAZINES; AND NOVEL BICYCLIC PYRAZINES AND PROCESSES FOR THEIR PRODUCTION.   (-R5)(-R6)(-R7)(-R8)   (Y&lt;(-(CH2)2-(5-R2,6-R1-PYRAZIN-2,3-YLENE)-CH2-))(-R3)(-R4)   PROCESSES FOR ALTERING THE FLAVORS OF CONSUMABLE PRODUCTS, INCLUDING FOODSTUFFS AND TOBACCOS, WHICH COMPRISE ADDING THERETO A SMALL BUT EFFECTIVE AMOUNT OF AT LEAST ONE BICYCLIC PYRAZINE HAVING THE FORMULA

United States Patent 3,686,177 BICYCLIC PYRAZINES HAVING FROM SIX T0 TENCARBON ATOMS IN THE HYDROCAR- BON RING Alan 0. Pittet, AtlanticHighlands, Michael E. Mason, Fair Haven, Ernst T. Theimer, Rumson, andMerrick S. Tibbetts, Colts Neck, N.J., assignors to InternationalFlavors & Fragrances Inc., New York, NY. No Drawing. Filed Apr. 14,1970, Ser. No. 28,528 Int. Cl. C07d 51/78 U.S. Cl. 260-250 R ClaimsABSTRACT OF THE DISCLOSURE Processes for altering the flavors ofconsumable products, including foodstuffs and tobaccos, which compriseadding thereto a small but effective amount of at least one bicyclicpyrazine having the formula l a R2 wherein Y is (-CH -)n, n is aninteger from 1 to 5, and R R R R R R R and R are the same or differentand represent hydrogen, or alkyl; the products so produced; flavoringand flavor-enhancing compositions containing such bicyclic pyraziues;and novel bicyclic pyrazines and processes for their production.

BACKGROUND OF THE INVENTION The present invention relates to bicyclicpyrazines and their use in processes and compositions for altering theflavors of various materials such as tobaccos, foodstuffs, and the like,as well as such novel pyrazines and processes for producing them.

Because of the tremendous consumption of foods, tobaccos, and othermaterials, there has been an increasing interest in substances andmethods for imparting flavors to such consumable materials. Thisinterest has been stimulated not only because of the inadequate quantityof natural flavoring materials available, but perhaps even moreimportantly, because of the need for materials which can combine severalnuances, will be more stable than natural materials, will blend betterwith other flavors or flavoring compositions components, and willgenerally provide superior products.

There have recently been suggestions that certain pyrazine derivativeshave flavors which might be useful in foods and other consumablematerials. For example, tetramethylpyrazine has been suggested for usewith vanillin in chocolate flavors, acetylpyrazine has been used intobacco and foods, and methoxypyrazine has been said to impart anut-like flavor to foods. Pyrazino[b]cyclopentanes have also beensuggested.

THE INVENTION It has now been found that heretofore unknown bicyclicpyrazines are capable of imparting a wide variety of flavors to variousconsumable materials. Briefly, the invention contemplates altering theflavors of such consumable materials by adding thereto a small buteffective 3,686,177 Patented Aug. 22, 1972 amount of at least onebicyclic pyrazine having the wherein Y is (CH -)n; n is an integer from1 to 5, inclusive; and R R R (R R R R and R represent hydrogen or alkyland are the same or different. The invention also contemplates flavoringand flavor-enhancing compositions containing such bicyclic pyrazines, aswell as the novel pyrazines and the processes for pre paring them.

More specifically, the bicyclic pyrazines according to this inventionare pyrazines to the b side of which is fused a sixto ten-memberedhydrocarbon ring. Such ring can be substituted with one or more alkylgroups, and the pyrazine ring can also be substituted with one or twoalkyl groups. In some instances one or the other of the rings can besubstituted with an alkadienyl group. It will be appreciated from thepresent disclosure by those skilled in the art that one or more pairs ofthe alkyl groups substituent on the hydrocarbon ring can be geminal,i.e., can be attached to the same ring carbon atom. It is generallypreferred in practicing the present invention that the substituents behydrogen or a lower alkyl group, particularly one having from one tothree carbon atoms.

A particularly preferred bicyclic pyrazine for use herein is5,6,7,S-tetrahydroquinoxaline having the formula This clear to yellowishliquid has nut-like strong cereal, fried corn-like odor and flavorcharacteristics, as further described hereinafter.

The lower alkyl derivatives of this material have interesting flavor andodor character and include S-rnethyl- 5,6,7,8 tetrahydroquinoxaline,2-ethyl-5,6,7,8-tetrahydroquinoxaline, 2-methyl-7-propyl 5,6,7,8tetrahydroquinoxaline 5,-6-diethy1 5,6,7,8 tetrahydroquinoxaline, 5,7-dimethyl 5,6,7,8 tetrahydroquinoxaline, and the like. Thus, for example,2,3 dimethyl-5,6,7,S-tetrahydroquinoxaline is obtained according to thepresent invention as a colorless crystalline material having atobacco-honey aroma. 5,7,7 trimethyl 5,6,7,8 tetrahydroquinoxaline is aliquid having a pleasant honey, tobacco flavor, whilepyrazino[b]cyclodecane is a yellowish liquid having a peanut andcracker-like flavor character.

The novel bicyclic pyrazines prepared according to the present inventioncan be obtained by a number of reaction routes, as by reacting 1,2diaminocyclohexane or monoalkylor polyalkyl-substituted 1,2diaminocyclohexane with glyoxal (a dioxoalkane) or l-alkyl or 1,2-dialkyl derivatives thereof, e.g., 2,3 butandione, under ring-closingconditions, or by reacting a 2 halocyclohexanone with ethylene diamine(a vicinal diaminoalkane) or a l-alkyl or 1,2-dialkyl derivativethereof, e.g. 2,3-diaminobutane, or by reacting an aliphaticethylenediamine or an alkyl or 1,2-dialkyl derivative thereof with a1,2-cyclohexadione or a monoor polyalkyl derivative thereof. Thebicyclic hydro pyrazine compounds obtained upon ring-closure is thendehydrogenated as necessary to provide the fused pyrazine ring.

Analogous compounds containing sevento ten-membered rings fused to thepyrazine ring are prepared similarly utilizing 1,2-diaminocycloheptaneor monoor polyalkyl derivatives thereof instead of thediaminocyclohexanes with the dioxoalkane, or utilizing2-halocycloheptanone or its monoalkyl or polyalkyl derivatives withethylene diamine or its derivatives instead of 1,2-diaminocyclohexane,or utilizing 1,2-cycloalkadione or monoor polyalkyl derivatives thereofwith ethylene diamine or its derivatives instead of cyclohexadione.Thus, for example, either (1) a 1,2-diaminocyclohexane or -cycloheptaneand the dioxo compound or (2) a 2-halo-cyclohexanone or -cycloheptanoneand a vicinal diaminoalkane are admixed preferably below C. to formrespectively, in case (1) above the dihydropyrazino[b]cyclohexane or,the dihydropyrazino[b]cycloheptane and in case (2) above, thetetrahydropyrazino[b]cyclohexane and thetetrahydropyrazino[b]cycloheptane and double bond isomers thereof.

Examples of the 1,2-diaminocycloalkanes are:

1,2-diaminocyclohexane; 1,2-diamino-4,S-dimethylcyclohexane;1,2-diamino-3,3,5,S-tetramethylcyclohexane; 1,2-diamino-3,4,4-triethylcyclohexane;1,2-diamino-3,3-dimethyl-4,4-diethylcyclohexane;1,2-diaminocycloheptane; 1,2-diamino-S-methylcycloheptane;

1,2-diamino-3 ,3 ,5 ,5 -tetramethylcyclohexane;1,2-diamino-3,3-dimethyl-5,S-diethylcycloheptane; and1,2-diamino-3,7-dimethylcyclodecane,

Examples of the 2-halo-cycloalkanone are: 2-chlorocyclohexanone;2-bromocyclohexanone; 2-chloro-3,4-dimethylcyclohexanone;2-chloro-3,3,5,5-tetramethylcyclohexanone; 2-bromocycloheptanone;Z-bromo-3,4,S-triethylcycloheptanone;2-bromo-3,4,5,6-tetramethylcycloheptanone; and2-chloro-S-methylcyclodecanone.

Examples of the 1,2-cycloalkadiones capable of being utllized hereinare:

In reaction involving dioxoalkanes or halocycloalkanones, thetemperature of the reaction is desirably below 10 C. to preventdecomposition of the dihydropyrazine to unwanted by-products.Temperatures below 80 C. are not necessary and can require excessivetime for completion of the reaction. It is accordingly desirable to usetemperatures from about 80 to 10 C. and it is preferred to utilizetemperatures of from about 30 C. to -15 C. For reactions involving1.2-cyclokadiones, vehicle reflux temperatures are utilized.

After the formation of the dihydropyrazine bicyclic compound, it isoxidized to provide the corresponding pyrazine derivative. This iscarried out at an alkaline pH obtained by adding a strong alkali metalhydroxide or an equivalent material such as an alkali metal carbonate.The hydroxides of sodium or potassium are desirably used.

The hydroxide-containing mixture is then treated with oxygen at atemperature of from 20 to 50 C. to provide a satisfactory reaction ratewhile minimizing undesirable side reactions and the ebullition of thereactants. The oxygen can be pure or can contain inert diluents. Air canbe used as the oxygen source.

The oxygen is added to the reactants by sparging or otherwise bubblingthe gas through the reaction mixture. At the temperatures used herein,the times for the reac- 75 tion range from about 30 minutes to 24 hours,and it is desirable to carry out the reaction such that it attains ahigh degree of completion in from about one to three hours.

The reaction is desirably carried out in an inert reaction vehicle toreduce polymer formation, to permit better control over the reactiontemperature, and to improve mixing of the reactants. The preferred inertreaction vehicles are solvents and include alkanols, preferably loweralkanols such as methanol, ethanol and the like.

After the reaction is completed, as readily determined by gaschromatography, the pH of the reaction mixture can, if desired, bereduced by the addition of an acid, desirably a strong mineral acid suchas dilute sulfuric acid, preferably 10% to 50% sulfuric acid. If anyundissolved hydroxide exists at this point then it is preferred that itbe removed, as by centrifugation or filtration. The crude bicyclicpyrazine is then stripped of vehicle and further purified as desiredaccording to the procedures hereinafter described.

The ratio of diaminocycloalkane to the glyoxal or of cycloalkadione todiaminoalkane can be stoichiometric, but better yields are frequentlyotbained with amounts of glyoxal or diaminoalkane in up to 10% excess ofstoichiometric. It will be appreciated by those skilled in the art thatuse of 1,2-diamino-3-ethylcyclohexane with glyoxal will provide 5 ethyl5,6,7,8 tetrahydroquinoxaline and reaction of 1,2-diaminocyclohexanewith diacetyl will provide 2,3-dimethyl-5,6,7,S-tetrahydroquinoxaline,and so The tetrahydroquinoxaline according to the present invention canalso be prepared by oxidation and subsequent acidification of l,2,3,4tetrahydrophenazine to form tetrahydroquinoxaline dicarboxylic acid orthe alkali metal salt thereof and pyrolysis of the acid or salt to thequinoxaline.

The initial oxidation reaction is carried out with a strong oxidizingagent such as aqueous alkali metal permanganate, desirably potassiumpermanganate. In order to obtain good yields without unduly longreaction times, the reaction is desirably carried out at temperatures ofat least about C. In the aqueous solution at atmospheric pressure thisreaction can be carried out at temperatures of about 100 C., althoughhigher temperatures are possible at superatmospheric pressures. Thedesirable temperature range for use herein is accordingly from about 75C. to 100 C., and temperatures from C. to C. are preferred.

After ring cleavage with the oxidizing agents, the manganese dioxideprecipitate obtained is filtered, centrifuged, or otherwise removed fromthe aqueous solution (which aqueous solution contains substantially allof the product of reaction) and Washed several times with water torecover all traces of the product which has the structure:

The dicarboxylate-containing solution is then acidified with an acid,desirably a strong mineral acid such as sulfuric, hydrochloric, and thelike, to precipitate the dicarboxylic acid. Hydrochloric acid is apreferred mineral acid. The acidified material is then concentrated toremove water.

The dicarboxylic acid is recovered by filtration and pyrolyzed at fromto 300 C. to provide the pyrazine. The pyrolysis is discontinued whenthe reaction is completed, as evidenced by cessation of CO evolution.

It will be understood by those skilled in the art that the intermediateand the final products prepared herein are neutralized, washed, anddried to obtain the desired substances. The novel bicyclic pyrazines canbe obtained in purer form or in substantially pure form by conventionalpurification techniques. Thus, the products can be purified and/ orisolated by distillation, extraction, crystallization, preparativechromatographic techniques, and the like. It has been found desirable topurify the bicyclic pyrazines by fractional distillation under vacuum,

It will be appreciated from the present disclosure that the bicyclicpyrazines and mixtures thereof according to the present invention can beused to alter, vary, fortify, modify, enhance, or otherwise improve theflavor of a wide variety of materials which are ingested, consumed, orotherwise organoleptically sensed. Such pyrazines are accordingly usefulin flavoring compositions and in flavorenhancing compositions. Aflavor-enhancing composition is taken to mean one which contributes apart of the overall flavor impression by supplementing or fortifying anatural or artificial flavor in a material.

When the bicyclic pyrazines of this invention are used in a flavoring ora flavor-enhancing composition, they can be combined with conventionalflavoring materials including organic acids such as fatty, saturated,unsaturated, and amino acids; alcohols, including primary and secondaryalcohols; esters; carbonyl compounds including ketones and aldehydes;lactones; other cyclic organic materials including benzene derivatives,alicyclics, heterocyclics such as furans, pyridines, other pyrazines andthe like; sulfur-containing materials including thiols, sulfides,disulfides and the like; proteins; lipids; carbohydrates; socalledflavor potentiators such as mono-sodium glutamate, quanylates, andinosinates; natural flavoring materials such as cocoa, vanilla, andcaramel; artificial flavoring materials such as vanillin; and the like.

It will be appreciated from the present description that the types andamounts of materials selected from the foregoing groups of materialswill depend upon the precise oragnoleptic character desired in thefinished product and, especially in the case of flavoring compositionsused to enhance other flavors, will vary according to the foodstuff towhich flavor and aroma are to be imparted. Inorganic materials such assodium chloride and freshness preservers such as butylatedhydroxyanisole and propyl gallate can be added for their adjuvant orpreservative effects on the flavoring composition.

The bicyclic pyrazines, or the compositions incorporating them, asmentioned above, can be combined with one or more vehicles or carriersfor adding them to the particular product. Vehicles can be edible orotherwise suitable materials such as ethyl alcohol, propylene glycol,water, and the like. Carriers include materials such as gum arabic,carrageenen, other gums, and the like. The pyrazines can be incorporatedwith the carriers by conventional means such as spray-drying,drum-drying, and the like. Such carriers can also include materials forcoacervating the pyrazines (and other flavoring ingredients, as present)to provide encapsulated products. When the carrier is an emulsion, theflavoring composition can also contain emulsifiers such as monoanddiglycerides of fatty acids and the like. With these carriers orvehicles the desired physical form of the composition can be prepared.

It will be understood by those skilled in the art that the bicyclicpyrazines can be added to the materials to be flavored at any convenientpoint in the production of the finished product. Thus, when the bicyclicpyrazines are used to alter or otherwise vary the fla'vor of afoodstuff, they can be added in the original mixture, dough, emulsion,batter, or the like prior to any cooking or heating operation.Alternatively, they can be added at a later stage of processing ifvolatilization losses would be excessive during the earlier processing.

When the materials are used to treat tobacco products, for example, theadditive can be applied in a suitable manner by spraying, dipping, orotherwise. The pyrazines can be applied during the casing or final spraytreatment of the tobacco, or they can be applied at some earlier stageof curring. The quantity of *bicyclic pyrazines or mixtures thereofutilized should be sufiicient to impart the desired flavorcharacteristic to the product, but on the other hand, the use of anexcessive amount of the pyrazines is not only wasteful and uneconomicalbut in some instances too large a quantity may unbalance the flavor orother organoleptic property of the product to be consumed. The quantityused will vary depending upon the ultimate foodstulf, tobacco product,or other consumable product; the amount and type of flavor initiallypresent in the product; the further process or treatment steps to whichthe product will be subjected; regional and other preference factors;the type of storage, if any, to which the product will be subjected; andthe pre-consumption treatment, such as baking, frying, and so on, givento the product by the ultimate consumer.

It is accordingly preferred that the ultimate compositions contain fromabout 0.1 part per million (p.p.m.) to about 100 ppm. of bycyclicpyrazines. More particularly, in food compositions it is desirable touse from about 0.1 to about 20 ppm. and in certain preferred embodimentsof the invention, from about 1 to about 15 p.p.m. of the pyrazines areincluded in the finished product. On the other hand, tobaccocompositions can contain as little as 0.1 p.p.m. and as much as 100p.p.m., depending upon whether a cigarette tobacco, a pipe tobacco, acigar tobacco, a chewing tobacco, or snuff is being prepared. All parts,proportions, percentages, and ratios herein are by weight unlessotherwise indicated.

The amount of bicyclic pyrazines or pyrazines to be utilized inflavoring or flavor-enhancing composition can be varied over a widerange depending upon a particular quality to be added to the foodstuff,tobacco, or other consumable material. Thus, amounts of one or morebicyclic pyrazines according to the present invention from about 0.1 upto or can be incorporated in such compositions. It is generally found tobe desirable to include from about 0.5 to about 25% of the bicyclicpyrazines in such compositions.

The following examples are given to illustrate embodiments of theinvention as it is presently preferred to practice it. It will beunderstood that these examples are illustrative, and the invention isnot to be considered as restricted thereto except as indicated in theappended claims.

EXAMPLE I Preparation of 5,6,7,8-tetrahydroquinoxaline plete, thereaction mixture assumes a milky, heterogeneous appearance.

The mixture is then stirred for two hours at 20 C., whereafter 40 g. ofpotassium hydroxide pellets are added. Oxygen is passed through thehydroxide-containing mixture for one hour at -20 C., and the temperatureis then raised to 4050 C. after which oxygen is passed through for anadditional hour. During the higher temperature portion of the oxygenaddition the color of the reaction mass changes successively from milkythrough clear yellow to orange-yellow to darker orange-brown.

The vehicle is recovered in a Buchi evaporator. The brown residue fromthe evaporator is flash-distilled at 75-88 C. and 4.0-2.0 mm. Hg toobtain a yellow liquid. The 50.2 g. of product in 3000 m1. of hexane isthen fed to a chromatography column loaded with 1000 g. of 80- 200 meshacidified alumina. The column is then successively eluted with 3000 ml.of 25% ether-75% hexane, and with 2000 ml. of 40% ether-60% hexane toobtain a total of 30.0 g. of 5,6,7,8-tetrahydroquinoxaline product.

Proton magnetic resonance (PMR) analysis of the product in carbontetrachloride shows a broad singlet at 1.92 p.p.m. (four protons on acyclohexane ring in the beta position from a pyrazine ring), a broadsinglet at 2.90 p.p.m. four protons on a cyclohexane ring alpha to apyrazine ring, and a singlet at 8.38 p.p.m. attributable to two protonson a pyrazine ring. Infrared (IR) analysis shows absorptions at 3014,1405, 1154, 1175, 990, 930, 905, 855, and 830 cm- Ultraviolet (UV)spectral analysis shows absorptions at 210, 274, and 285 nm.

Mass spectroscopy of the material at an inlet temperature of 150 C.,magnet current of 380 ma., ionizing current of 5 1a and a 70-voltionizing potential shows:

Net Mass] peak charge height Preparation of5,6,7,S-tetrahydroquinoxaline A three-necked flask fitted withcondenser, mechanical agitator, thermometer, and dropping funnel ischarged with 6.0 g. of 1,2,3,4-tetrahydrophenazine in 125 ml. of waterand heated to 90 C., and a solution of 37.0 g. of potassium permanganatein 100 ml. of water is added during an hour while the temperature ismaintained at 8090 C. The flask contents are stirred for an additionalone-half hour, cooled to 7075 C., and filtered.

The residue is slurried in hot water and filtered three times. Thefiltrates are concentrated to a volume of 200 ml. and acidified with 17ml. of concentrated hydrochloric acid. The liquid is then evaporated,and the resulting dicarboxylic acid precipitate is then pyrolyzed in ashortpath distillation unit at 200-250 C. at 5 mm. Hg pressure tosubstantially pure 5,6,7,8-tetrahydroquinoxaline.

The aroma of the tetrahydroquinoxaline as perceived from a blotter stripdipped in its alcoholic solutions is oil-fried corn chip fragrance witha potato chip character at the 0.1% level and an earthy popcorncharacter at the 1.0% level.

The odor of a 1 p.p.m. solution in water is like fried corn chips, andthe taste is like corn chips with a light aftertaste, somewhatreminiscent also of a peanut flavor. At 0.2 p.p.m. in water there is asweet taste with a light bitter aftertaste. The taste at 0.2 p.p.m. in aaqueous sugar solution is like that of fresh milk with sweet milkchocolate, popcorn, peanut butter, earthy, and coconut flavor notes.

Tested in beef broth at 4 p.p.m., the tetrahydroquinoxaline seems todeepen the spice notes and enhances this aspect of the flavor. At 0.5p.p.m. in chicken broth, the compound adds burning spice notes. Suchcharacteristics fit it for a wide variety of uses as a flavor enhancerand for milk, cream, popcorn, fried corn chips, peanut, hazelnut,chocolate, and coconut flavors and aromas.

EXAMPLE III Preparation of 2,3dimethyl-5,6,7,S-tetrahydroquinoxaline Athree-liter Morton flask equipped with agitator, thermometer, condenser,addition funnel, gas dispersion tube, and cooling means is charged with57.0 g. (0.5 mol) of 1,2-diaminocyclohexane in 1700 cc. of ethanol andcooled to 20 C. During a 20-minute period a solution of 43.0 g. (0.5mol) of 2,3-butanedione in 100 cc. of ethanol is added, the flaskcontents turning milky-white upon such addition. The flask contents arethen stirred for 45 minutes at 20 C After this additional stirring iscompleted, 20.0 g. of potassium hydroxide is added, and oxygen issparged through the mixture for one hour at 20 C. The sparging iscontinued for 45 minutes as the temperature is permitted to rise to 0C., whereupon the solution assumes a light brown color, and then for 50minutes at 40 C. The ethanol is then removed from the clear, dark brownsolution under reduced pressure.

The residue after the described ethanol removal is poured into 750 cc.of water and extracted thrice with 250 cc. portions of hexane. Thehexane extracts are washed twice with equal volumes of saturated aqueoussodium chloride and dried over magnesium sulfate, and the hexane isrecovered under reduced pressure. The 56.1 g. of material so obtained isdistilled in a Vigreaux column with no reflux to obtain 26.1 g. of afraction at a pot temperature of C. and a vapor temperature of 75 C. ata pressure of 0.35 mm. Hg.

The aforesaid fraction in the amount of 7.4 g. (0.045 mol) is refluxedwith 5.0 g. of potassium hydroxide in 200 cc. of ethanol. The ethanol isthen evaporated, and the residue is taken up in ethyl ether. Thepotassium hydroxide is filtered off, and the crude material ischromatographed on 250 g. of aluminum oxide (acid). The column is elutedwith 250 cc. of hexane and with 500 cc. of 40% ether-60% hexane toprovide 3.5 g. of material.

The 3.5 g. is rechromatographed on g. of aluminum oxide (acid). Elutionwith cc. of hexane provides no material. Subsequent elution with 500 cc.of 40% ether-60% hexane provides 1.76 g. of 2,3-dimethyl-5,6,7,8-tetrahydroquinoxaline. This material is a colorless crystallinesolid having a tobacco-honey odor and a melting range of 52.2-55.8 C.The structure is confirmed by IR, PMR, and mass spectroscopy.

Other 2,3dialkyltetrahydroquinoxalines or 2-alkyl-tetrahydroquinoxalinescan conveniently be similarly prepared by utilizing respectviely1,2-dialkyl glyoxals or 1- alkylglyoxals instead of 2,3-butadione.

EXAMPLE IV Preparation of 5,6,7,8-tetrahydroquinoxaline A 250 ml. flaskequipped with a thermometer, magnetic stirrer, condenser, and additionfunnel is charged with 7.2 g. of ethylene diamine and ml. of diethylether and cooled to 50 C. Then 13.2 g. of 2-chloro cyclohexanone in 10ml. ether is added during 15 minutes with agitation, and the flaskcontents are stirred for an additional two hours. Fourteen grams ofpotassium hydroxide is added and the flask contents are warmed to 3 C.

Air, dried by passage through sulfuric acid, is passed through thereaction mixture for 2.5 hours at 3 C. The reaction mixture is thenheated under reflux for an additional one hour and 10 minutes andfinally cooled. The course of the oxidation is followed by the gaschromatographic analysis of samples withdrawn from the reaction mixtureat various time intervals.

After standing, the reaction mixture is filtered to remove solids andthe ether vehicle is stripped off to leave a solid which is distilledunder high vacuum using a short path distillation column. The materialobtained at 85 C. and 1 mm. Hg is further fractionated by gaschromatography to yield pure 5,6,7,8-tetrahydroquinoxaline.

EXAMPLE V Preparation of 5,7,7 -trimethyl-5 ,6,7,8-tetrahydroquinoxaline A mixture of 6 g. (0.1 mol) of ethylcnediamine,15.4 g. (0.1 mol) of 2-hydroxy-3,5,5-trimethyl-2-cyclohexenl-one, 1 g.of p-toluenesulfonic acid, and one liter of benzene is refluxed for fivehours in a three-liter flask fitted with a Bidwell-Sterling distillationreceiver. During the refluxing, 3.5 ml. of water is collected.

After refluxing is completed, the solvent is stripped off, and theresidue is dissolved in 300 ml. of ethanol. The alcoholic solution issaturated with oxygen for one hour at 20 C., sparged with oxygen for onehour at 4048 C., and cooled; and the alcohol is stripped off. Theresidue after stripping is mixed with 5 g. of petroleum oil andvacuum-distilled.

The trimethyltetrahydroquinoxaline is obtained as a liquid having aboiling point of 105 C. at 1.6 mm. Hg and the structure:

This material at the 0.6 p.p.m. level in water has a woody, fruitycharacter; at 1 p.p.m., a nougat, honeylike character; and at 2 p.p.m. ahoney, nougat character with a burning taste. The material isparticularly interesting for use in honey, tea, nougat, and berryflavors, and is useful in tobacco flavoring compositions.

EXAMPLE VI Preparation of pyrazino- [b]-cyclodecane Ten grams (0.06 mol)of 1,2-cyclodecadione is refluxed with 4 g. of ethylene diamine, oneliter of benzene, and 1 g. of p-toluene sulfonic acid for 2.5 hours. Thewater formed during the reaction is trapped out, and 2.3 mil. iscollected. During the refluxing the deep yellow color changes to a lightorange color.

The reaction mixture is then cooled, and the benzene is stripped off.Ten grams of the product is dissolved in 300 ml. of ethanol and 4 g. ofpotassium hydroxide is added. The mixture is cooled to 20 C., and oxygenis passed vigorously through the solution for one hour. The mixture isthen warmed to 50 C. and oxygen sparging is continued for one hour. Themixture is thereupon cooled, the ethanol is stripped off, and theresidue is mixed with Primol petroleum oil and distilled under vacuum.

The pyrazino[b]cyclodecane is obtained as a yellow liquid having aboiling point of ll-1l2 C. at 0.6 mm. Hg and the structural formula Thishas a taste at 1 p.p.m. in water of fat-fried onion; at 10 p.p.m. afat-fried aroma with aftertaste of fresh onion; and at 20 p.p.m. a greenvegetable aroma with a fried fat aftertaste. It can be used to providecereal and heated flavor character to consumable products.

EXAMPLE VII Cheddar cheese flavor formulation A cheddar cheese flavoringformulation is prepared by admixing the following ingredients in theamounts indicated:

Tetrahydroquinoxaline, produced in Example I 5 The foregoing cheeseformula is incorporated into a bland cream cheese and, when tested oncrackers, is found to have an excellent, sharp cheddar cheese flavor.

EXAMPLE VIII Beef soup The following beef soup-flavoring composition isprepared:

Ingredient: Amount (parts) Salt 33.00 Hydrolyzed vegetable protein 23.94Monosodium glutamate 14.63 Sucrose 13.33 Autolyzed yeast powder 4.00Onion powder 6.00 Beef extract flavor (Example XVI of U.S. Pat.

3,394,016) Caramel color powder 2.00 Celery seed powder 0.27 Whitepepper powder 0.13

Five ounces of the foregoing mix is added to 8 ounces of boiling waterto produce a soup with a beef flavor. This preparation is repeated witha second five-ounce portion in 8 ounces of boiling water to which isadded 10 p.p.m. of the tetrahydroquinoxaline prepared in Example II. Thesecond preparation containing the tetrahydroquinoxaline is judged tohave an improved flavor and aroma with more roast beef flavor character.

EXAMPLE IX A beef-flavored gravy is prepared by combining the followingmaterials:

The foregoing ingredients are homogenized and then autoclaved and a beefgravy is obtained. When 10 p.p.m. of the quinoxaline of Example 11 isadded, a more pronounced beef flavor character is obtained.

EXAMPLE X A confection center is prepared from the followingingredients:

Ingredient: Amount (parts) Peanut butter 300 Ground sweet cracker meal100 Confectioners sugar 200 Shortening 25 When 5 p.p.m. of thequinoxaline of Example II is added to the confectionary centercomposition, a fuller richer flavor character is obtained.

EXAMPIJE XI A commercially available peanut butter is modified tocontain 5 p.p.m. of the tetrahydroquinoxaline produced according to thepresent invention, and the modified peanut butter is tested against theunmodified peanut butter (that is, the peanut butter without addedquinoxaline).

In panel comparisons of unmodified commercial peanut butter with themodified peanut butter, the modified peanut butter is consistentlyselected as having a greater peanut butter aroma intensity and a greaterpeanut taste intensity, with a significance factor of at least ascalculated by chi-square probability.

EXAMPLE XII Bacon-flavor powder A material useful for providing a baconflavor to foodstuffs is prepared by admixing the following ingredients:

Ingredient:

After the foregoing mixture is prepared '10 p.p.m. of5,6,7,8-tetrahydroquinoxaline is added, and the mixture is spray-driedin 2. Bowen spray-drier. The tetrahydroquinoxaline is described asimparting a nut-like flavor note to the bacon flavor.

What is claimed is:

1. A bicyclic pyrazine having the formula R3 R4 N Bl wherein Y is (-CH-)n; n is an integer from 1 to 5, inclusive; and R R R R R R R and R arethe same or difierent and represent hydrogen or lower alkyl having oneto three carbon atoms and wherein the pyrazine is not monomethylsubstituted.

2. A bicyclic pyrazine according to claim 1 wherein 5 n is 1 and R R R RR R R and R are hydrogen.

3. A bicyclic pyrazine according to claim 1 wherein n is 1, R and R aremethyl, and R R R R R and R are hydrogen.

4. A bicyclic pyrazine according to claim 1 wherein n is 1, R and R aremethyl groups substituent on the ring carbon atom immediately above Y, Ris a methyl group substituent on the other carbon atom adjacent to Y,and R R R R and R are hydrogen.

5. A bicyclic pyrazine according to claim 1 wherein n is 5 and R R R R RR R and R are hydrogen.

References Cited UNITED STATES PATENTS 1/1967 Wendt et a1. 260-250 R3/1967 Wendt et a1. 260-250 R 4/1968 Wendt et al. 260-250 R 3/1969 Wendtet a1. 260-250 R '12/1969 Wendt et a1. 260-250 R FOREIGN PATENTS 3/ 1969Netherlands 260-250 8/1962 Germany 260-250 :NICHOLAS S, RIZZO, PrimaryExaminer U .S. Cl. X.R.

